Background:Scientific research in axial spondyloarthritis (axSpA) over the recent years has grown significantly. Early detection, diagnosis and treatment are critical to improve the functioning situation, reduce comorbidities and loss of quality of life of patients with axSpA. However, the diagnostic delay remains high.Objectives:To describe the path to diagnosis among Russian axSpA patients.Methods:The European Map of Axial Spondyloarthritis (EMAS) was a cross-sectional on-line survey of unselected patients with self-reported axSpA conducted in 13 European countries. Russian participants were recruited between December 2017 and February 2018 through the Russian Ankylosing Spondylitis Association and an online panel. Socio-demographics, age at symptom onset, age at diagnosis, diagnostic tests performed, HCPs visited prior diagnosis, and diagnosing HCP were collected. Diagnostic delay was calculated by subtracting the age at symptom onset from age at diagnosis.Results:233 Russian participants were enrolled. The mean age was 36.7±9.1 years, 51.9% were female. The average duration of the disease was 12.4±9.5 years. 54.9% patients visited more than one specialist before diagnosis. Russian respondents reported a low demand for GPs, physiotherapist and an orthopaedic specialist in contrast to the total of EMAS participants (table 1). AxSpA was most frequently diagnosed by a rheumatologist (87.5%).Table 1.Health professional visited before being diagnosed with axSpA.Russian population N=233Pan-European population N=2706%%GP67.8183.4Rheumatologist44.2166.1Other37.3413.6Orthopaedic specialist23.6134.5Physiotherapist17.646.0Osteopath13.7316.3Most used medical test for diagnosis are similar to those used in the aggregated Pan-European sample (table 2).Table 2.Medical tests made to diagnose axSpA.Russian population N=230Pan-European population N=2661%%X-rays80.8772.3MRI scan70.0064.3HLA B2762.6165.4CT scan25.2220.8Ultrasound scan17.8321.0Radionuclide scintigraphy3.516.4Other9.134.2Among those who underwent HLA-B27 test (n=144), 87.23% declared to be HLA-B27 positive. This percentage is higher than that found in the Pan-European aggregated sample (73.95% of HLA-B27 positive).The mean age at symptom onset was 24.22±9.75 years. Consequently, the mean diagnostic delay calculated was 6.88±6.94 years without differences between males and females and the median was 5 years. More than half of the sample had a calculated diagnostic delay of higher than 5 years (55.39%).Conclusion:The results of the survey confirm the existence of a diagnostic delay. Although this aspect has been greatly improved in recent years, reducing diagnostic delay is one of the major challenges associated with the clinical management of axSpA and must be addressed with GPs and rheumatologists. We suggest that features in patient routing in other countries can be explained these differences: the survey did not include a neurologist, to whom patients with back pain have a visit in Russia. The most frequently performed medical tests are included in the ASAS criteria for axSpA, which indicates a good knowledge of doctors.Disclosure of Interests:Svetlana Lapshina: None declared, Marco Garrido-Cumbrera: None declared, Tatiana Dubinina Speakers bureau: Novartis, BIOCAD, MSD, Pfaizer, Abbvie, UCB, Alexander Dubikov: None declared, Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: Pfizer, Novartis, AbbVie, JSC BIOCAD, Сelgene, MSD, Sanofi, Maxim Korolev: None declared, Elena Zonova Speakers bureau: Pfizer, Abbvie, Bayer, Janssen, Lilly, Polina Pchelnikova: None declared, Alexey Sitalo: None declared, Irina Shipilova Employee of: Novartis Pharma LLC

Axial spondyloarthritis (axSpA) has been shown to impact patients’ (pts) professional opportunities, employment status and work productivity [1].To evaluate employment status, work-related issues and their interrelation with the disease-related characteristics among Russian axSpA pts.The European Map of Axial Spondyloarthritis (EMAS) was a cross-sectional on-line survey of pts with self-reported axSpA conducted in 13 European countries. Russian participants were recruited between Dec 2017 and Feb 2018 through the Russian Ankylosing Spondylitis Association and an online panel. Socio-demographic, BASDAI, psychological distress (GHQ-12), working status and work-related issues (e.g. taking sick leave, difficulties fulfilling or reducing working hours, etc.) were assessed.233 Russian pts participated in EMAS. The mean age was 36.7±9.1 years, 51.9% were female, and the mean disease duration was 12.4±9.5 years. Of the 233, 226 reported their employment status and productivity, of which 73.45% were employed, 12.39% were unemployed, 4.42% were on sick leave, 3.54% were homemakers, 2.21% were retired, 2.21% were on early retirements, 1.77% were students. Of the 160 pts, who reported their occupation, 73 (45.63%) were employed and had jobs requiring higher education qualifications, 39 (24.38%) had management positions, 23 (14.38%) were skilled manual workers and 12 (7.50%) were skilled non-manual workers, 3 (1.88%) were occupied in armed forces, 3 (1.88%) pts worked as unskilled workers. 124 (76.54%) of 162 pts survey respondents declared to have suffered work issues related to their disease in the 12 months prior to the survey. The most common work-related issue was difficulty fulfilling working hours in 69 (56.56%), followed by taking sick leave 49 (40.16%) and asking for days off 44 (36.07%) out of 122 pts. Pts who reported any type of issues at work had higher BASDAI and psychological distress (GHQ-12 score) (table 1).145 (76.32%) out of 190 responded pts reported that their choice of workplace had been influenced by the disease (68.25%).Table 1.BASDAI and GHQ-12 by work-related issues and difficulty fulfilling working hours due to axSpA.Any type of issue at workBASDAIGHQ-12MeanSDNMeanSDNNo3.14*1.93382.95*3.3938Yes4.97*2.081246.53*3.76124Difficulty fulfilling working hoursMeanSDNMeanSDNNo4.53**2.15555.49**3.8055Yes5.32**1.96697.36**3.5469* Mann-Whitney test p-values < 0.001** Mann-Whitney test p-values < 0.05Results from the Russian sample of the EMAS survey highlight the impact of axSpA in working life. Patients with any type of work-related issue mark above the cut-off point of BASDAI and GHQ-12, so work-related issues are associated to a status of high disease activity and a risk of poor mental health. Among all work-related issues surveyed, the presence of presenteeism (measured by difficulty fulfilling working hours) is associated to both a clinical and significant increase in disease activity through BASDAI.[1]van Lunteren, M., et al.https://doi.org/10.1093/rheumatology/kex365.Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: Pfizer, Novartis, AbbVie, JSC BIOCAD, Сelgene, MSD, Sanofi, Marco Garrido-Cumbrera: None declared, Tatiana Dubinina Speakers bureau: Novartis, BIOCAD, MSD, Pfaizer, Abbvie, UCB, Alexander Dubikov: None declared, Elena Zonova Speakers bureau: Pfizer, Abbvie, Bayer, Janssen, Lilly, Maxim Korolev: None declared, Svetlana Lapshina: None declared, Polina Pchelnikova: None declared, Irina Shipilova Employee of: Novartis Pharma LLC, Alexey Sitalo: None declared

Aim to identify outdated terms and make changes to the terminology of spondyloarthritis.MATERIALS AND METHODS:At the first stage of the work, the terms divided into two categories: "outdated" definitions and terms that need to be improved or unified. Subsequently, each member of the Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia (ExSpA) presented by its own definition of the designated term or agreed with the previous term. At the next stage, the existing definitions were put together. After discussion, experts left a term that scored at least 2/3 of the votes. The special opinion of experts was recorded, whose did not coincide with the majority opinion. An open vote was conducted, when defining an "outdated" term with the unanimous decision of all group members, this term was not recommended for further clinical use.RESULTS:The work carried out allowed us to identify a number of terms that are not recommended for use in clinical practice. Number of terms are defined, which should be used when discussing the problem of spondyloarthritis.CONCLUSION:The Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia suggests using or, accordingly, not using a number of terms and their definitions in clinical practice.

The paper summarizes the data available in the literature and those from the authors' studies on the molecular and cellular mechanisms of apoptosis and their state in rheumatoid arthritis (RA). Impaired apoptotic processes in RA are one of the causes of synovial cell hyperactivation that leads to the increased inflammatory process, synovial hyperplasia, and progression of the disease as a whole. The most important feature of a cellular continuum in the affected synovial fluid is the coexistence of just two mechanisms that control apoptosis: 1) a traditional activation mechanism leading to progressive joint inflammation and destruction and 2) an inhibitory mechanism implemented through the expression of proapoptotic molecules. The apoptotic factors are a useful tool for assessing the prognosis of RA and a promising target for pharmacotherapy.

Objective: to describe the portrait of a patient with rheumatoid arthritis (RA) in real clinical practice, to assess disease activity from the point of view of a physician and a patient, functional status, quality of life (QOL), and the efficiency of the therapy performed.Patients and methods. The investigation enrolled 976 RA patients from a cohort of patients in the TERMINAL-I multicenter study, who, when visiting a rheumatologist, independently assessed the disease activity and QOL using a computer system (the «Computer Terminals of SelfAssessment for Patients with Rheumatic Diseases» project). The mean age of the patients was 52.30±13.3 years; women accounted for 85%; the median disease duration 8.0 [4.0; 14.0] years. Baseline clinical parameters and pharmacotherapy were evaluated for 6 months. The disease activity was determined by the DAS28 and RAPID-3 indices; functional status and quality of life were evaluated by the HAQ and the EQ-5D, respectively.Results. 83% of the RA patients were positive for rheumatoid factor and 60% were for anti-cyclic citrullinated peptide antibodies. There was a preponderance of patients with high (40.5%) and moderate (46.8%) RA activity; 6.9% were observed to have a low activity; 5.8% had clinical remission. The mean values of DAS28 and RAPID-3 were 4.7±1.3 and 13.7±3.6, respectively. Only 14.3% of patients had a good functional status that was comparable with the population-based control (HAQ≤0.5). The remaining patients were found to have a substantial decrease in joint functional parameters (median HAQ 1.88 [1.0; 2.5]) and EQ-5D QOL (0.60 [0.60; 0.74). Prosthetic joints were present in 7.4% of patients. At visit 1 to a rheumatologist, the therapy was changed in 15% of patients. During 6-month follow-up, conventional disease-modifying anti-rheumatic drugs were taken by almost all (91.2%) patients. Of them, 70.9% of the patients were treated with methotrexate (MTX): 77.0% received the latter at a dose of 15 mg/week and 23.0% had it at a dose of >15 mg (17.5 to 40 mg/week). Glucocorticoids could be stopped in 20.5% of the patients within six months. Tumor necrosis factor-α inhibitors and anti-B-cell therapy were used in 6.6 and 16.2% of patients, respectively. At 6-month follow-up (Visit 2), 54% of patients achieved a 20% clinical improvement in the ACR criteria. At the same time, the DAS28 scores decreased substantially from 4.5±1.2 to 3.8±1.1 (p = 0.0001). There was a minimal functional improvement in the HAQ index in 64% of patients and a better EQ-D QOL scores in 16%.Conclusion. The majority of RA patients who came to the rheumatologists showed high to moderate disease activity. This was due to long disease duration, inadequate MTX dose, and insufficient patient monitoring in real clinical practice. Introduction of a computer system for selfassessment of their health status by RA patients in an outpatient setting could improve the interaction of physicians, nurses, and patients, better monitor disease activity, and enhance therapeutic efficiency.

The paper gives the definition of remission in axial spondyloarthritides (axSpA), which has been developed by the Spondyloarthritis Study Group of Experts. The work used the Delphi technique. At stage 1, based on the analysis of the data available in the literature and on their own clinical experiences, the experts proposed some variants of the definition of remission and ways of its evaluation in patients with axSpA. At Stage 2, the definitions that had received at least 80% of the votes via anonymous voting were selected and adopted without further discussion. Those that had received an equal number of votes were reconsidered and additionally discussed; then there was repeat voting, by choosing the final definition. As a result of their discussion, the experts formulated the definitions of clinical laboratory and magnetic resonance imaging (MRI) remissions. They proposed the following remissions in axSpA: drug and drug-free, clinical laboratory, and MRI remissions, as well as a remission in the presence and absence of structural changes in the locomotor system, as evidenced by imaging techniques. Criteria for clinical laboratory remission and basic tools for its evaluation that can be used in real clinical practice and researches have been elaborated.

Background Currently a number of risk factors (RF) are considered to be responsible for radiological progression of knee osteoarthritis (OA), nevertheless key predictors of OA progression have not yet been established. Objectives To identify RF predicting radiological progression of knee joint osteoarthritis (OA) in a 5 year multicenter prospective study. Methods This study of RF predicting knee OA progression was the first with multicenter prospective design ever conducted in Russia. The study included 344 female patients 40–75 y.o with primary stage I-III knee OA (ACR criteria) from 6 centres. Radiological stage was identified by Kellgren J.- Lawrence J. grading scale. The follow up (FUP) was 5 years. Individual patients’ files described 90 parameters. Instrumental diagnostic methods included plain radiography of knee joints, dual energy X-ray absorptiometry (DEXA) of lumbar spine L1–4, femoral neck and subchondral tibia, ultrasound (US) and MRI examination of knee joints. OA progression was verified based on evolution of radiological stage. At baseline 24 pts (7%) had stage I OA, 227 (66%) – stage II, and 93 (27%) – stage III. Discriminant analysis was applied to verify most reliable RF predicting radiological progression. Results Radiological progression was documented in 45% participants during 5 year FUP. The groups with and without progression were comparable in terms of age and disease duration (»<0,05). Pts who progressed suffered more intensive knee pain – 68(52–72) vs 41(30–63) mm, » <0,01, had higher body weight – 82(77–93) vs 72(65–81) kg, » <0,01, had higher rates of knee synovitis (US) 44% vs 26%, »=0,03, (RR=1,67, 95% CI 1,07–2,59) and mid-tibia bone marrow oedema – 60% vs 28%, » <0,01 (RR=2,12, 95% CI 1,34–3,35). The discriminant analysis showed that knee pain, excessive body weight, synovitis and mid-tibia bone marrow oedema (MRI) can be considered as predictors of OA radiological progression. A model capable of predicting OA course in an individual patient with high 88% accuracy, 87.7% sensitivity and 70% specificity has been developed based on identified RF and their coefficients. Area under the ROC-curve 0, 921 (95% CI 0,875–0,966). Conclusions Knee pain, excessive body weight, synovitis and bone marrow oedema should be considered as key RF predicting knee OA radiological progression. Disclosure of Interest None declared

The paper gives recommendations for the drug therapy of axial spondyloarthritides, which have been developed by the Spondyloarthritis Study Group of Experts. The recommendations describe the patient management tactic in the most common clinical situations, which is aimed at maximizing the efficacy and safety of treatment.

Aim: To evaluate the efficacy and safety of amtolmetin guacyl in the management of osteoarthritis (OA) of knee and associated dyspepsia in routine clinic setting. Methods: In an observational study conducted in the OA outpatients between February 2015 and December 2015, patients with knee joint (KJ) pain ≥ 40 mm on visual analogue scale (VAS) and dyspepsia were enrolled. Amtolmetin guacyl 600 mg tablets twice daily was administered for up to 28 days. Patients were evaluated at baseline, Day 14 ± 3, and at Day 28 ± 3 for severity of pain in “target” knee (VAS), Western Ontario and Mc master Universities Arthritis (WOMAC) pain and stiffness, and severity of dyspepsia assessment (SODA). Results: Of the 219 OA patients, approximately 72.5% patients reported decrease in pain in the target KJ by ≥ 40% at the end of the study. Mean pain reduced from 65 mm at baseline to 27 mm at the end of the study. A significant decrease in WOMAC pain score, morning stiffness, and functional limitations were also observed (P<0.001). A significant decrease in severity of dyspepsia assessment (SODA) score and increase in satisfaction was observed. Amtolmetin tolerability was comparatively better than previously used NSAIDS. Conclusion: Amtolmetin guacyl is effective and safe in OA patients with associated dyspepsia and has comparatively better tolerability than other NSAIDS. This trial is registered with http://clinicaltrials.gov, number NCT02865161.

The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm for the management of knee osteoarthritis (OA), published in December 2014, provides practical guidance for the prioritization of interventions. This current paper represents an assessment and endorsement of the algorithm by Russian experts in OA for use in Russian clinical practice, with the aim of providing easy-to-follow advice on how to establish a treatment flow in patients with knee OA, in support of the clinicians’ individualized assessment of the patient. Medications recommended by the ESCEO algorithm are available in Russia. In step 1, background maintenance therapy with symptomatic slow-acting drugs for osteoarthritis (SYSADOA) is advised, for which high-quality evidence is provided only for the formulations of patented crystalline glucosamine sulphate (pCGS) (Rottapharm/Meda) and prescription chondroitin sulfate. Paracetamol may be added for rescue analgesia only, due to limited efficacy and increasing safety signals. Topical non-steroidal anti-inflammatory drugs (NSAIDs) may provide additional symptomatic treatment with the same degree of efficacy as oral NSAIDs but without the systemic safety concerns. To be effective, topical NSAIDs must have high bioavailability, and among NSAIDs molecules like etofenamate have high absorption and bioavailability alongside evidence for accumulation in synovial tissues. Oral NSAIDs maintain a central role in step 2 advanced management of persistent symptoms. However, oral NSAIDs are highly heterogeneous in terms of gastrointestinal and cardiovascular safety profile, and patient stratification with careful treatment selection is advocated to maximize the risk: benefit ratio. Intra-articular hyaluronic acid as a next step provides sustained clinical benefit with effects lasting up to 6 months after a short-course of weekly injections. As a last step before surgery, the slow titration of sustained-release tramadol, a weak opioid, affords sustained analgesia with improved tolerability.

The paper gives the recommendations for the assessment of disease activity and functional status in patients with ankylosing spondylitis in clinical practice, which have been developed by experts, by taking into account international and Russian experience in managing these patients.

Resolution of the Council of Experts on «The place of phosphodiesterase-4 inhibitor in the combination treatment of moderate to severe psoriasis and active psoriatic arthritis».

The paper gives recommendations for the drug therapy of axial spondyloarthritides, which have been developed by the Spondyloarthritis Study Group of Experts. The recommendations describe the patient management tactic in the most common clinical situations, which is aimed at maximizing the efficacy and safety of treatment.

Aim. To estimate the rate of articular cartilage microcrystallization in osteoarthritis (OA). Subjects and methods. The investigation included 110 people who had undergone total endoprosthetic replacement for coxarthrosis. A total of 50 patients with total hip endoprosthetic replacement for femoral neck fractures were recruited as a comparison group. An X-ray diffractometer was used to detect crystals. Results. Cartilage mineralization was seen in 72% of the patients with late-stage OA. Conclusion. Articular cartilage microcrystalline stress is a constant sign of late-stage OA requiring further clinical interpretation.

The paper provides guidelines for the use of tumor necrosis factor- α (TNF- α ) inhibitors in the treatment of patients with axial spondyloarthritis  (axSpA), including ankylosing spondylitis. It gives data on the efficacy of TNF- α inhibitors in patients with non-radiographic axSpA. By using international and Russian guidelines, the authors lay down indications for this therapy and criteria for evaluation of its efficiency and safety.